DISPOSITION OF ALPRAZOLAM IN HUMAN VOLUNTEERS - DIFFERENCES BETWEEN GENDERS

The disposition of alprazolam in 16 young healthy volunteers (eight females and eight males) was investigated. All volunteers were given a 1 mg dose of alprazolam. Dose/kg was 13.3-mu-g/kg (SD +/- 0.89-mu-g/kg) on average for male volunteers and 17.5-mu-g/kg (SD +/- 1.84-mu-g/kg) for the female volunteers. Pharmacokinetic parameters were calculated separately for both sexes in order to detect possible gender-dependent differences. The elimination rate constant (beta) for alprazolam proved to be significantly higher in the female population 0.067 hr-1 vs. 0.053 hr-1 (p = 0.03). The closely related parameters, elimination half-life (t1/2) and clearance (Cl) were also significantly different. The total area under the serum concentration curve (AUC(tot)), maximum serum concentration (cm(max)) and volume of distribution (Vd) were not significantly different. AUC(tot) corrected for differences in dose/kg was on the other hand significantly higher in males (p = 0.003) while c(max) corrected in the same manner was not.